How sponsors should be rethinking quality and oversight for decentralized clinical trials

At Curebase, we believe that clinical trials can be transformed to include every patient and physician in the research process, regardless of geography. That mindset is all the more important now that traditional site-based research is largely stalled, with sites redirecting almost all of their resources to COVID-19 trials and travel lockdowns preventing routine study visits.

Sponsors are moving very quickly to adopt virtual research techniques Organizations of all types have quickly incorporated telemedicine, mobile phlebotomy, and other decentralized tools to keep studies going during a challenging time.

In our experience, however, these adaptations carry significant risks if they are not approached with some fundamental new thinking about quality and oversight of the trial. While we are excited that the industry is warming up to more patient-centric methods, we also know that study sponsors will struggle to preserve data quality if decentralized methods are applied as band-aids to traditional trial designs, without fundamentally new thinking and new software capabilities to power it.

Prefer to learn via webinar? You can register now for our webinar on quality and oversight, happening June 11, 2020, where you can hear from us and our panel.

Clinical research is irrelevant without quality

We’ve spent a lot of time (basically all of our time since we founded Curebase) advocating for decentralized clinical trials, and quality has always been our focus. It’s not too difficult to send a mobile phlebotomist to a patient’s home and perform a blood draw. But to ensure that the home-health experience is equivalent to an in-person visit at a leading academic hospital, and produces equivalent data… that is where the challenge comes into play.

In the home health example, let’s say a study has LDLs as a primary endpoint. When a sponsor contracts a phlebotomy vendor and sends them to the patient’s home, it’s critical to know:

• Did the patient fast?
• What time did the blood draw take place?
  

In a naive approach, this would rest on simple documentation produced by the phlebotomist, who asks the patient if he or she fasted, and then documents the time of the blood draw. This however has some room for error.

For one, patients can misrepresent whether or not they fasted. Secondly, the phlebotomist may forget to ask the question, or if asked, may document it incorrectly. And lastly, the actual time the blood draw was performed could be backdated.

There are a couple of solutions here. One is a conventional solution focused on training, and the other is a more novel approach based on data and software. Before I dive in though, I will provide some background on how quality is derived in typical site-based trials, and why it doesn’t scale to tackle this challenge.

In conventional clinical trials, site staff is the focal point for ensuring quality

In conventional research, sites are responsible for enrolling patients and ensuring that they adhere to the study protocol. The site engages with patients, performs procedures, and captures most of the study data to share with the sponsor -- traditionally on paper, now mostly through electronic data capture. ePRO has of course been around for a long time now, but the site is still the focal point of data collection and quality in most trials.

“Study sponsors will struggle to preserve data quality if decentralized methods are applied as band-aids to traditional trial designs without fundamental new thinking.”

Since the site is operating almost the entire study and capturing all the data, it is by far the most critical component and the largest point of failure. So, in this world, clinical trials are ALL about site selection. Not enrolling fast enough? You picked the wrong sites. Patient retention is low? The sites aren’t properly resourced. Poor data quality? The sites aren’t experienced, or need more training.

This framework works very well for most study designs, but poses a challenge when major elements of a trial are at-home, and barriers between the site and patient are widened.

Take the mobile phlebotomy example. Typically, sponsors classify mobile phlebotomists and home health providers as vendors, meaning that they are not actually on the delegation of authority log. They also have weaker communication with the site that enrolled the patient, and furthermore, the company providing the home-health service will have numerous employees and/or contractors in many regions who can’t possibly be continuously retrained in the same capacity that a research site can be.

This is why training and site selection isn’t a sufficient toolkit for quality in new trial designs.

To create an oversight framework, decentralized trials can utilize a highly centralized virtual “site” to oversee remote aspects of the study and ensure quality.

At Curebase, one of our key research innovations has been the utilization of a central virtual research site. This site looks just like your typical research site, but it engages patients regardless of geography utilizing telemedicine and software tools, and has staff communicate fully electronically.

The site includes everything you would except in a site:

• A principal investigator
• Subinvestigators, if needed
• Research coordinators
  

The central virtual site also performs core responsibilities, such as:

• Maintaining site files
• Delegation of authority log
• IRB communication
• Completing case reports
• Responding to queries

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The central site increases oversight while fitting coherently into existing multi-site models and use existing sites to maximum impact.

At Curebase, we are not actually advocates for siteless research. Instead, on each of our studies, we work with a network of clinical research sites that include everything from community PCPs and first-time researchers to established research institutions, depending on the study needs. Working with sites enables access to clinical expertise, access to patients, and access to critical equipment, while preserving the patient-physician relationship to create a safe, trustworthy research environment.

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All that said, in each our of our studies we prefer to include a central “virtual” research site in addition to the regional sites, and we do this for a few reasons.

First off, decentralized clinical trials have extremely complex logistics compared to fully on-site trials. Coordinating home visits, home sample shipments, and even just the basics of arranging video calls with patients and completing case reports virtually create many opportunities for error and deviation from study protocols.

In a multi-site study, many of the logistics of decentralization can shifted onto a central site. This site becomes the expert in facilitating these aspects of the study, and they don’t need to be delegated to the regional centers. For example, mobile phlebotomy visits can be coordinated and receive QA by the central site. ePayments and remote consenting can optionally be moved to the central site as well, along with whichever responsibilities benefit most from centralization.

This framework has many befits:

• Sites focus on their highest-impact responsibilities. These include recruiting and treating patients, ensuring the rights and welfare of those patients, staying vigilant for safety events, and performing procedures and tests when patients visit their facilities.
• Sponsors reduce their training burden. Sponsors don’t need to educate and re-educate dozens of facilities on complex logistical, remote processes, which is time-consuming and more likely to yield protocol deviations.
• Variability is reduced by centralizing operations. With a single body overseeing remote processes, there is less room for protocol deviations and hidden variables that could emerge with remote processes fully delegated to dozens of institutions.

Oversight is not possible without unified data, and sponsors need to invest in tools that provide real-time access to clinical and operational context.

The caveat to this framework is that the central, virtual site assumes a very large responsibility. Like any site, the central site becomes accountable to the rights and wellbeing of the patient, to GCP, FDA regulations, and to maintaining the quality of data. This is nearly impossible without real-time access to study data in a completely digital form, to ensure the remote investigator can genuinely understand the context of the patient and maintain their oversight role.

At Curebase, we use a single software platform to power our studies, which allows us to present 100% unified clinical and operational to our remote investigators. This is, in our experience, imperative if a remote site is able to perform their responsibilities. To have complete sense of the patient in a decentralized study, investigators need to know:

• Interactions between the patient and regional sites and/or healthcare providers
• Interactions with home health providers
• Lab results
• Self-reported patient data
• Data from patients’ EMRs
• Data from smart devices
  
  

This is why we built Curebase in the first place, and it’s been a key ingredient to implementing our processes that not just decentralize research, but do so in a way that enables quality and oversight by a central site.

How to learn more?

This is the first in a series of educational blog posts on decentralizing research at high quality. We’ve barely scratched the surface here, and topics still to come will build on how this foundation -- a strong central site model and unified data platform -- allows us to implement new innovative quality and oversight processes. Subscribe to our blog series to get updates as we deep dive into our methodologies for decentralizing research. Also look into our webinar series, where we meet with panelists to go in depth on each of these topics.

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Our Full- Service DCT Vendor Guide also offers great resources into how quality can be established within a study with the help of a DCT vendor.